Release of salicylic acid, diclofenac acid and diclofenac acid salts from isotropic and anisotropic nonionic surfactant systems across rat skin

Release of salicylic acid, diclofenac acid, diclofenac diethylamine and dic lofenac sodium; from lyotropic structured systems, namely; neat and middle liquid crystalline phases, across mid-dorsal hairless rat skin into aqueous buffer were studied. Release results were compared with those from the iso tropic systems. The donor systems composed of the surfactant polyoxyethylen e (20) isohexadecyl ether, HCl buffer of pH 1 or distilled water and the sp ecific drug. High performance liquid chromatography (HPLC) methods were use d to monitor the transfer of the drugs across the skin barrier. Results ind icated that the rate-determining step in the transport process was the rele ase of the drug from the specified donor system. Further, apparent zero ord er release was demonstrated with all systems. Except for diclofenac sodium, drug fluxes decreased as the donor medium changed from isotropic to anisot ropic. The decrease in fluxes was probably due to the added constrains on t he movement of drug molecules. By changing the anisotropic donor medium fro m neat to middle phase, drug flux decreased in case of salicylic acid and d iclofenac sodium. In the mean time, flux increased in case of the diethylam ine salt and appeared nearly similar in case of diclofenac acid. Rates of d rug transfer across the skin from the anisotropic donors seemed to be large ly controlled by the entropy contribution to the transport process. The typ e and extent of drug-liquid crystal interactions probably influenced the la tter. (C) 2001 Elsevier Science B.V. All rights reserved.